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What are HRB? How human-adapted bifidobacteria work in the gut microbiome

Looking to maximise the number of years spent in good health, consumers are turning to preventative measures in a new era of healthy ageing.

This transitional mindset is reshaping the industry. While longevity remains a key goal, the shift towards prevention suggests that maintaining vitality and independence in later years is what is truly driving consumer behaviour.

This has led to an increased focus on the microbiome and how it can influence health. The microbiome is a vast collection of all microbes – such as bacteria, fungi, viruses, and their genes – that naturally live in the body. As the microbiome is the key interface between the body and the environment, these microbes can affect health in many ways – including how the body responds to environmental influences.1

Thanks to next-generation sequencing, research has accelerated, leading to countless microorganisms being identified. The colonic microbiome is now considered to have a community of roughly 40 to 100 trillion microorganisms spanning hundreds of species.

Among these microorganisms are bifidobacteria, key health-associated members of the human gut microbiome. Bifidobacterial species are assumed to have coevolved with humans and include members that are naturally present in the human gut, thus recognised as Human-Residential Bifidobacteria (HRB).2

Bifidobacteria differ depending on their host species e.g., primates, rodents, birds, insects. Currently, more than 100 species of bifidobacteria have been identified, and can be classified as followed by their habitats:

HRBs in infants: B. breve; B. bifidum; B. infantis; and B. longum

HRBs in adulthood: B. adolescentis; B. pseudocatenulatum; B. angulatum; and B. longum

Non-HRB in other species: B. animalis; B. lactis; B. thermonphilum; B. magnum

Types of Human-Residential Bifidobacteria

History of HRB

First discovered in 1899, HRB are more like “evolutionary partners” that have accompanied humans throughout time. In fact, reports suggest that HRB have co-evolved alongside humans for millions of years, fundamentally shaping biology and digestive systems.2

Bifidobacteria have been our partners for over 15 million years

Bifidobacteria have developed a diverse number of genetic strategies to adapt to their respective hosts and display differences in their ecological adaptation among species. HRB specifically possess unique genetic elements and superior physiological functions that contribute to their ecological fitness and competitiveness, therefore are thought to be more beneficial to humans.2

Their long-term adaption to distinct environments over time had led to diversification of HRB, and in turn has positioned HRB as natural partners for humans, providing a strong axis for probiotic product concepts.

Why HRB are important

Humans are exposed to microbes immediately after birth which rapidly seed the gut microbiome. This exposure starts when the baby travels through the birth canal, with additional exposure during breastfeeding.

This initial exposure is essential as development of the microbiome plays a key role in training the infant’s immune and digestive system, while also protecting against metabolic and inflammation concerns.

Woman breastfeeding baby

Although microbes are crucial for development, bifidobacteria have a more difficult, highly selective entry into the infant microbiome as they are carefully curated by breast milk.

Breast milk contains an exclusive diet of human milk oligosaccharides (HMOs) which are specific nutrients that serve as a biochemical gatekeeper, filtering out non-adapted bacteria while allowing only specialized Bifidobacterium strains to thrive. HRB can be considered “special” bifidobacteria that have passed this selection.

This is thanks to one major difference observed in HRB genomes: they possess carbohydrate (metabolism) related genes, also associated with HMOs in breast milk. In growth studies conducted in breast milk HRBs showed growth, whereas many non-HRB strains decreased below the detection limit.3

Changes throughout lifespan

HRB abundance in the gut is thought to change throughout the lifespan. In infancy, presence of HRB are particularly high as they are specially adapted to break down breast milk. After weaning, HRB presence begins to decrease but remains stable in adulthood. And in older years, abundance decreases further, leaving a less diverse, more imbalanced gut microbiome behind.

Considering the natural decline of HRB, numerous studies have been conducted to analyse supplementation of different HRB strains, with specific focus on age-specific effects.

B. longum BB536 (one of the longum strains detected across many generations) is reported in clinical studies to have a strong bowel regulating effect, and suggests interactions with other gut microbes. In a study containing 34 adults over a 17-day period, participants took either yoghurt with BB536 (100g/day – equalling 2bn CDU/day) or placebo.4

Consumption of yoghurt with BB536 showed an increased butyrate-producing bacteria in the gut and tryptophan (Trp) metabolites in stool. Trp that reaches the large intestine is metabolised by gut bacteria into indoles and tryptamine. This is significant as these compounds act as chemical messengers in the gut-brain axis and support the gut barrier, helping to maintain a healthy mucosal immune response.

Subsequently, the study results suggest that the HRB strain has a beneficial effect on regulating the intestinal environment.

Bifidobacteria in the large intestine

While HRB have generally been considered to be age-restricted, recent studies have tested their impact on different generations. For example, while B. breve has generally been an infant-associated HRB species, a study investigated its effects on older generations.

The study involved participants suspected of mild cognitive impairment (MCI) aged 50 to under 80, with results showing a significant improvement of Cognitive Function Score after 16-week supplementation of B. breve MCC1274 (20bn CFU/day).

These results have the potential to change industry narrative, showing “infant-specific” HRBs may be able to help in later life – potentially capturing attention of health-conscious consumers who are focusing on healthy ageing.

Spreading the word

While HRB are generally well known to microbiologists, they are less known to the general public compared to generic probiotics. This is largely because commercial supplements often use dairy-sourced strains rather than human-specific strains.

To help spread the word, Morinaga Milk Industry Co. Ltd., developed the HRB logo. The aim of the logo is to express the idea that humans are connected to the HRB through the intestines, symbolised by its central design.

Morinaga Milk Industry's Human-Residential bifidobacteria logo

“This logo is designed to help our customers clearly communicate the value of HRB through a consistent and trusted identity,” says Saki Yamashita, global marketing manager at Morinaga Milk Industry.

“Positioning HRB as ‘natural partners for human health’ provides a powerful and credible foundation for probiotic product development, storytelling and consumer communication – rooted in science, history and human biology.

“We see strong potential for HRB to contribute to the future of health and wellness by enabling science-based solutions that support people at different life stages, including but not limited to healthy ageing,” adds Yamashita.

As microbiome science advances, HRB are emerging as the next-gen of probiotics. This positioning is particularly relevant in the context of healthy ageing where consumers are looking to seek targeted, preventative solutions. Morinaga Milk has positioned itself at the forefront of this shift, working to invite the next-phase of microbiome-based innovation for long-term health.

Impact of gut health on the body

Find out more here about how HRB can help to shape the future of healthy ageing.

References

  1. National Institute of Environmental Health Sciences. Microbiome.
  2. Wong, CB.; et al. Insights into the reason of Human-Residential Bifidobacteria (HRB) being the natural inhabitants of the human gut and their potential health-promoting benefits. FEMS Microbiol Rev. 2020 May 1;44(3):369-385.
  3. Wong, CB.; et al. Different physiological properties of human-residential and non-human-residential bifidobacteria in human health. Benef Microbes. 2018 Jan 29;9(1):111-122.
  4. Ejima R.; et al. The Impact of Fermented Milk Products Containing Bifidobacterium longum BB536 on the Gut Environment: A Randomized Double-Blind Placebo-Controlled Trial. Nutrients. 2024 Oct 22;16(21):3580.

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